In silico Evaluation of Plant-Derived Phytochemicals as Potential Inhibitors of Acetyl-CoA Acyltransferase: A Comparative Study with the Drug Sandoz 58-035 in Lipid Metabolism Disorders
Author(s): Jharna Maiti, Amit Joshi* and Shivam Mishra
Abstract
Lipid metabolic disorders are increasingly recognized as major contributors to cardiovascular diseases, obesity, and related metabolic complications worldwide. Although conventional drugs such as Sandoz-58-035 (CAS 78934-83-5) are widely used to control lipid levels, their long-term administration is often associated with adverse effects, highlighting the need for safer therapeutic alternatives. In the present study, an integrated in silico approach was employed to evaluate plant-derived phytochemicals as potential inhibitors of acetyl-CoA acyltransferase, a key enzyme involved in lipid metabolism. A total of 51 phytochemicals obtained from Bryophyllum pinnatum, Ocimum tenuiflorum, Camellia sinensis, and Tinospora cordifolia were screened using molecular docking analysis. Several compounds demonstrated strong binding affinity toward the target enzyme, with binding energies superior to the reference drug, indicating enhanced inhibitory potential. The top-performing phytochemicals were further subjected to pharmacokinetic evaluation using ADME analysis, which revealed favourable absorption, high gastrointestinal availability, and minimal toxicity risks. To validate the stability and dynamic behaviour of the enzyme-phytochemical complexes, molecular dynamics simulations were conducted, confirming stable interactions over the simulation period. Comparative analysis with Sandoz-58-035 drug further supported the effectiveness of selected phytochemicals. Overall, the findings suggest that these natural compounds could serve as promising and safer alternatives for the management of lipid metabolism disorders.